Autism is a developmental disorder that exhibits retardation in development of sociality and communication skills. In Japan, it is said that an incidence of autism is 1 to 2 in every 1000 people, though this figure may vary depending on how to define a scope of autism. According to announcements from Autism Society Japan, it is estimated that 360,000 people across Japan are affected by autism, and that 1.2 million people have autism when including high functioning autism (Asperger disorder) and the like, which are not accompanied by mental retardation or speech disturbance.
Various causes such as lack of affection, brain disorders, and environmental factors (mercury accumulation) have been proposed as to development of autism. Currently, the most widely accepted theory is that a genetic predisposition is responsible for autism, and many genetic factors are considered to participate therein. For information, schizophrenia, which is supposedly regarded as a genetic disease, affects both monozygotic twins with an incidence of 50%. By contrast, autism affects both monozygotic twins with an incidence of 90%, and familial clustering thereof is also observed.
For example, it has been reported that a HOXA1 gene is highly probably associated with development of autism (Ingram et al., Teratology. 2000 December; 62 (6): 393-405). HOXA1, which is a transcription factor-encoding gene located on chromosome 7, has been found to be important for neuronal differentiation and development. Autistic individuals have a high probability of mutations seen in repeat polymorphism sites in this gene. In addition, it has also been reported that genes associated with autism with developmental regression are located on chromosome 7 and chromosome 21 (Molloy et al., Mol Psychiatry. 2005 August; 10 (8): 741-746).
Recently, attention has been paid to association of pituitary hormone oxytocin with psychiatric disorders. Oxytocin, which is a 9-amino-acid long peptide hormone, has been known to have effects of promoting lactation and promoting uterine contraction, and its receptors are also present in central nervous system and present even in males. For example, it has been reported that some autistic individuals have lower plasma oxytocin levels (Modahl et. al. Biol. Psychiatry. 1998 February; 43 (4): 270-277) and that oxytocin receptor-knockout mice exhibit social behavior abnormalities (Takayanagi et al., Proc Natl Acad Sci USA. 2005 Nov. 1; 102 (44): pp 16096-16101). Fehr et al. have reported that when 194 students received intranasal administration of oxytocin or placebo and then played an “investment game”, the group receiving oxytocin invested more money and more frequently invested a maximum allowable than the placebo group (Kosfeld et al., Nature. 2005 Jun. 2; 435 (7042): pp 673-676). This result indicates that administration of oxytocin increases trust in others and individual's willingness to accept risks, that is, oxytocin promotes prosocial behaviors.
CD38, a 45-kDa single-transmembrane protein, is an ectoenzyme whose catalytic activity (NAD degrading activity) is located on an extracellular domain. CD38 has been known to be expressed on activated T and B cells, NK cells, monocytes, plasma cells, and medullary thymocytes, and this expression has been considered to depend on differentiation and activation of the cells. CD38 is widely used as a marker in studies of T and B cell activation and also clinically utilized in diagnosis of hematologic malignancies and in diagnosis of autoimmune diseases, AIDS, and aplastic anemia. Other various reports have been made on the activity and nature of CD38, particularly in the field of control of immune responses. However, no document has reported its association with psychiatric disorders or oxytocin release.